TABLE 8

P2Y₆ receptor (previously known as P2Y purinoceptor 6, pyrimidinoceptor, and uridine nucleotide receptor) 2.1:NUCT:4:P2Y₆

	TM	aa	AC	Chr. Map	References
Human^*	7	328	NM_176797; NM_176798; NM_176796; NM_004154	11q13.5 (Somers et al., 1997)	Communi et al. (1996b)
Rat	7	328	NM_057124	1Q32	Chang et al. (1995)
Mouse	7	328	AF298899	N.A.	Lazarowski et al. (2001b)
Functional assays		Formation of IP₃ in 1321N1 cells that stably express recombinant receptor (Communi et al., 1996); rat C6—2B glioma cells that natively express the receptor (Nicholas et al., 1996)

Ligand	Action	Selectivity	Endogenous	References
UDP	Agonist	No	Yes	Communi et al. (1996b)
UDPβS	Agonist	Yes	No	Jacobson et al. (2002)
5BrUTP	Weak agonist	No	No	Communi et al. (1996b)
UTP	Weak agonist	No	Yes	Communi et al. (1996b)
ADP	Weak agonist	No	Yes	Communi et al. (1996b)
2-MeSATP	Weak agonist	No	No	Communi et al. (1996b)
PPADS	Antagonist	No	No	Robaye et al. (1997)
Reactive blue 2	Antagonist	No	No	Robaye et al. (1997)
MRS2567	Antagonist	Yes	No	Mamedova et al. (2004)
MRS2578	Antagonist	Yes	No	Mamedova et al. (2004)
MRS2575	Antagonist	Yes	No	Mamedova et al. (2004)
Agonist potencies	IP₃ formation: UDP (EC₅₀ = 300 nM) > 5BrUTP (EC₅₀ = 800 nM) > UTP (EC₅₀ = 6 μM) > ADP (EC₅₀ = 30uM) >> 2-MeSATP (EC₅₀ = 100 μM) (Communi et al., 1996b)
Antagonist potencies	Reactive blue 2 > PPADS > suramin (Robaye et al., 1997)
Radioligand assays	None
Radioligands	None
Transduction mechanism	G_q/G₁₁; PI hydrolysis (PLCβ activation) and elevated [Ca²⁺]_i in expression systems
Distribution	Northern blot: placenta, spleen, thymus, intestine (Communi et al., 1996b); vascular smooth muscle, lung (Ralevic and Burnstock, 1998); RT-PCR: human bone, two osteoblastic cell lines, brain-derived cell lines (Burnstock and Knight, 2004); quantitative RT-PCR: spleen, placenta, kidney (high levels), lung, intestine, adipose, bone, heart (moderate expression), and some brain regions (Moore et al., 2001)
Tissue function	Regulation of chemokine production and release in monocytes (Warny et al., 2001); NaCl secretion in colonic epithelial cells (Burnstock and Knight, 2004); role in proliferation of lung epithelial tumor cells (Schafer et al., 2003); role in mediating contractions of human cerebral arteries (Malmsjö et al., 2003b); interaction with the TNF-α-related signals to prevent apoptotic cell death (Kim et al., 2003b)
Phenotypes	None
Comments	Four transcript variants that encode the same isoform have been identified for this gene^*; a pseudogene was also described (Burnstock and Knight, 2004); rat and mouse homologs have also been cloned (Chang et al., 1995; Lazarowski et al., 2001b); rat, mouse, and human P2Y₆ receptors are UDP-selective, and UTP is less potent, whereas ATP is a very weak partial agonist; the P2Y₆ receptor has a pharmacological profile very similar to the UDP receptor on rat C6—2B glioma cells (Lazarowski et al., 1994b); rat P2Y₆ potently inhibited N-type Ca channels when expressed in sympathetic neurons, and receptor transcripts were reported to be present in brain tissues (Filippov et al., 1999)

aa, amino acids; AC, accession; chr., chromosome.